The Role of the Proteasome in Platelet Function

Abstract

Platelets are megakaryocyte-derived acellular fragments prepped to maintain primary hemostasis and thrombosis by preserving vascular integrity. Although they lack nuclei, platelets harbor functional genomic mediators that bolster platelet activity in a signal-specific manner by performing limited de novo protein synthesis. Furthermore, despite their limited protein synthesis, platelets are equipped with multiple protein degradation mechanisms, such as the proteasome. In nucleated cells, the functions of the proteasome are well established and primarily include proteostasis among a myriad of other signaling processes. However, the role of proteasome-mediated protein degradation in platelets remains elusive. In this review article, we recapitulate the developing literature on the functions of the proteasome in platelets, discussing its emerging regulatory role in platelet viability and function and highlighting how its functional coupling with the transcription factor NF-κB constitutes a novel potential therapeutic target in atherothrombotic diseases.

Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management

“…Fibrinogen is a 340-kDa plasma glycoprotein mainly synthesized by liver parenchymal cells [14,15]. The protein is also stored in the platelet alpha granules, thus providing a localized boost in fibrinogen concentration at sites of platelet activation [16]. Fibrinogen is synthetized as a hexamer composed of two copies of three homologous polypeptide chains (Aα, Bβ, and γ), interconnected by a complicated series of disulfide bonds [1,9].…”

“…A case study also described the successful use of a new oral anticoagulant (rivaroxaban) for the anticoagulant management in patient with afibrinogenemia and severe hypofibrinogenemia [12,88]. The treatment of thrombotic episodes is very demanding due to the high risk of bleeding [5,16]. Further studies are required to determine the optimal postoperative thromboprophylaxis in CFD.…”

The Proteasome Inhibitor Bortezomib Induces Apoptosis and Activation in Gel-Filtered Human Platelets

“…Platelets, like nucleated cells, have an active proteasome system [23,24]. Earlier, a study by Ostrowska et al showed that the human platelet 20S proteasome has a chymotrypticlike activity [25].…”

“…Subsequently, a global proteomic analysis has shown that platelets express all the three proteolytic activities of the proteasome: caspase-like, trypsin-like and chymotrypsin-like activities [26]. Although the role of platelet proteasome in protein degradation is not clear [23], its role in regulating platelet production [27] and lifespan [28] has been suggested.…”

Cell Therapy: Types, Regulation, and Clinical Benefits

“…Platelets are acellular fragments derived from maturing megakaryocytes and function mainly in maintaining primary hemostasis and thrombosis to preserve vascular integrity ( 219 ). Although predominated by platelets—reservoirs of multitudinous immunologic molecules, soluble proteins, and growth factors ( 220 )— and plasma components, PRP contains cellular components, such as leukocytes ( 217 ). Several commercially available kits can be used for PRP processing with varying outcomes in terms of platelet, red blood cell, and leukocyte concentrations ( 221 ).…”